Can Structure Therapeutics (GPCR) Reclaim 2025's Momentum in 2026?

The obesity drug market has become a battleground for innovation, with oral GLP-1 receptor agonists (GLP-1s) emerging as a transformative category. Structure Therapeutics' aleniglipron, an oral GLP-1 candidate, has captured investor attention after Phase 2b and exploratory Phase 2 ACCESS trials demonstrated robust weight loss outcomes. However, with a $4.8B valuation and a crowded competitive landscape, the question remains: Can Structure reclaim the momentum it gained in 2025 and justify its lofty expectations in 2026?

Clinical Differentiation: Efficacy and Safety

Structure's aleniglipron has shown compelling results in mid-stage trials. In the Phase 2b ACCESS study, the 120 mg dose achieved a placebo-adjusted mean weight loss of 11.3% at 36 weeks, with 86% of participants achieving at least 5% weight loss and 70% reaching 10% or more. Exploratory data from ACCESS II pushed this further, with the 240 mg dose showing 15.3% weight loss. These figures rival leading oral GLP-1s like Eli Lilly's orforglipron and Novo Nordisk's Wegovy oral formulation.

Safety remains a critical differentiator. Aleniglipron's tolerability profile aligns with the GLP-1 class, with gastrointestinal adverse events being the most common but no reports of drug-induced liver injury or QTc prolongation. A dose-escalation strategy, starting at 2.5 mg, has also improved patient tolerance. This contrasts with injectable GLP-1s, which face adherence challenges due to administration complexity.

Competitive Landscape: Oral GLP-1s and M&A Dynamics

The obesity market is intensifying. Novo Nordisk's oral Wegovy (25 mg) is awaiting FDA approval, while Eli Lilly's orforglipron is under regulatory review. Novo's recent $9B bid for Metsera-a clinical-stage obesity-focused biotech-underscores the sector's M&A frenzy, as major players seek to secure oral GLP-1 pipelines amid patent expirations of injectable blockbusters.

Structure's aleniglipron is positioned as a "second oral small molecule entrant", but its success hinges on Phase 3 validation. The company plans to initiate an end-of-Phase 2 meeting with the FDA in mid-2026 and advance to Phase 3 trials by the same timeframe. However, even with strong Phase 2 data, Structure must prove long-term efficacy and safety in larger trials to compete with established names.

Valuation Risks and Rewards

Structure's stock surged over 100% following the December 2025 data release, but a $4.8B valuation for a Phase 2b asset is ambitious. Analysts note that while aleniglipron's efficacy is "highly competitive," its commercial potential depends on head-to-head comparisons with orforglipron and Novo's dual GLP-1/amylin agonist. The obesity market's projected growth-driven by Medicare/Medicaid access expansions-offers upside, but Structure must navigate pricing pressures and payer negotiations.

Acquisition potential adds another layer of complexity. With biotech M&A activity surging in 2025, Structure could attract suitors seeking to bolster their obesity portfolios. However, its valuation already reflects a premium, and a failed Phase 3 trial or regulatory delay could trigger a sharp correction.

Conclusion: A High-Stakes Bet

Structure Therapeutics' aleniglipron has demonstrated the clinical promise needed to justify optimism. Its oral administration, dose-dependent efficacy, and favorable safety profile position it as a viable contender in a market where convenience and tolerability are key. Yet, the $4.8B valuation demands a successful Phase 3 trial and differentiation from Novo and Lilly's offerings.

For investors, the risks are clear: intense competition, regulatory uncertainty, and the inherent volatility of late-stage biotech speculation. However, the rewards are equally significant. If aleniglipron secures FDA approval and captures a meaningful share of the obesity market-or becomes an acquisition target-Structure could reclaim its 2025 momentum. The coming months will hinge on the company's ability to execute its Phase 3 strategy and navigate a rapidly evolving landscape.